Improved immunocytochemical methodology makes it possible to study human neurotransmitter specific systems with greater sensitivity and precision than hitherto possible. Studies have been initiated to complete mapping of the distribution of all tyrosine hydroxylase immunoreactive catecholamine neurons in the human central nervous system. Delineation of the adrenergic subgroup of these cells utilizing antibodies to phenylethanolamine N-methyltransferase is in an advanced stage. Application of antibodies to dopamine beta hydroxylase will permit distinction of dopaminergic and noradrenergic subgroups. The studies are being extended to include several neuropeptides which interact with catecholamine systems. The peptides chosen are neurotensin, substance P and enkephalin. A qualitative survey of the distribution of catecholamine and peptide neurons in the human infant brain is in an advanced stage. It will be used as a basis for quantitative studies of changes occurring in the numbers of perikarya and axons in these systems during development and aging. Particular attention will be paid to the populations of peptidergic and cholinergic neurons recently recognized in the human cerebral cortex and subcortical white matter, and to axon terminal patterns and densities in cerebral cortex, striatum, pallidum and substantia nigra. Such direct observations on the human brain are useful in assessing the degree to which evolution has occurred (a factor which effects the validity of extrapolation of experimental results in lower animals to humans), provide a basis for understanding human physiology, are of utility in interpreting results from non-invasive probes of neurotransmitter related function in the living human brain, give information regarding normal development and are a prerequisite to detection of alterations in pathological states. Parallel studies of Alzheimer's type dementias and Parkinson's disease will permit immediate application of results to study of human diseases.